Compounds of formula (I), ##STR4## are known compounds and can be used in the preparation of endothelin receptor antagonists as disclosed in EP 0713875A1 and WO 96/19459 in which compounds such as pyridin-2-yl-carbamic acid 2-[6-(5-isopropyl-pyridine-2-sulfonylamino)-5-(2-methoxy-phenoxy)-2-morpho lin-4-yl-pyrimidin-4-yloxy]-ethyl ester and 5-isopropyl-pyridine-2-sulfonic acid {6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-[2-(1H-tetrazol-5-yl)-pyridi n-4-yl]-pyrimidin-4-yl}-amide are incorporated.
Processes for the preparation of 2-halogeno-5-alkylpyridines have been disclosed in, e.g. EP-A-0 584 491 and EP-A-0 162 464.
By the process of the present invention, 2-halo-5-lower alkyl pyridines can be obtained in better yields and in less reaction steps. The invention relates to a novel process for the preparation of 2,5-disubstituted pyridines. More particularly the invention relates to the preparation of 2-halo-5-lower alkyl pyridines of the formula (I) ##STR5## wherein R.sup.1 denotes lower alkyl, and
X denotes halogen. PA1 a) reacting a compound of the formula (II) EQU R.sup.1 --CH.dbd.CH--R.sup.2 (II) PA1 a) reacting a compound of the formula (II) EQU R.sup.1 --CH.dbd.CH--R.sup.2 (II) PA1 a) reaction with chloracylnitrile, PA1 b) addition of hydrogen halide under water free conditions. PA1 a) reaction with thiourea to form 5-isopropyl-pyridine-2-thiol, PA1 b) reaction with chlorine to form 5-isopropyl-pyridine-2-sulfochloride, PA1 c) reaction with ammonium hydroxide to form 5-isopropyl-pyridine-2-sulfonamide, PA1 d) reaction with 4,6-dichloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidine to form 5-isopropyl-pyridine-2-sulfonic acid 6-chloro-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl-amide, PA1 e) reaction with sodium in ethylene glycol to form 5-isopropyl-pyridine-2-sulfonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-morpholin-4-yl-pyrimidin-4-yl -amide, PA1 f) reaction with pyridine-2-carbonyl azide to form pyridin-2-yl-carbamic acid 2-[6-(5-isopropyl-pyridine-2-sulfonylamino)-5-(2-methoxy-phenoxy)-2-morpho lin-4-yl-pyrimidin-4-yloxy]-ethyl ester. PA1 a) reaction with thiourea to form 5-isopropyl-pyridine-2-thiol, PA1 b) reaction with chlorine to form 5-isopropyl-pyridine-2-sulfochloride, PA1 c) reaction with ammonium hydroxide to form 5-isopropyl-pyridine-2-sulfonamide, PA1 d) reaction with 4-[4,6-dichloro-5-(2-methoxy-phenoxy)-pyrimidin-2-yl]-pyridine-1-oxide to form 5-isopropyl-pyridine-2-sulfonic acid 6-chloro-5-(2-methoxy-phenoxy)-2-(1-oxy-pyridin-4-yl)-pyrimidin-4-yl amide, PA1 e) reaction with sodium in ethylene glycol to form 5-isopropyl-pyridine-2-sulfonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(1-oxy-pyridin-4-yl)-pyrimidi n-4-yl amide, PA1 f) reaction with trimethylsilylcyanide and triethylamine to form 5-isopropyl-pyridine-2-sulphonic acid 2-(2-cyano-pyridin-4-yl)-6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-pyrimi din-4-yl-amide, PA1 g) reaction with ammonium chloride and sodium azide to form 5-isopropyl-pyridine-2-sulfonic acid {6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-[2-(1H-tetrazol-5-yl)-pyridi n-4-yl]-pyrimidin-4-yl}-amide. PA1 a) reaction with chloracylnitrile, PA1 b) addition of a hydrogen halide under water free conditions. PA1 a) reaction with thiourea to form 5-methyl-pyridine-2-thiol, PA1 b) reaction with chlorine to form 5-methyl-pyridine-2-sulfochloride, PA1 c) reaction with ammonium hydroxide to form 5-methyl-pyridine-2-sulfonamide, PA1 d) reaction with 4-[4,6-dichloro-5-(2-methoxy-phenoxy)-pyrimidin-2-yl]-pyridine-1-oxide to form 5-methyl-pyridine-2-sulfonic acid 6-chloro-5-(2-methoxy-phenoxy)-2-(1-oxy-pyridin-4-yl)-pyrimidin-4-yl amide, PA1 e) reaction with sodium in ethylene glycol to form 5-methyl-pyridine-2-sulfonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(1-oxy-pyridin-4-yl)-pyrimidi n-4-yl amide, PA1 f) reaction with trimethylsilylcyanide and triethylamine to form 5-methyl-pyridine-2-sulphonic acid 2-(2-cyano-pyridin-4-yl)-6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-pyrimi din-4-yl-amide, PA1 g) reaction with ammonium chloride and sodium azide to form 5-methyl-pyridine-2-sulfonic acid {6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-[2-(1H-tetrazol-5-yl)-pyridi n-4-yl]-pyrimidin-4-yl}-amide.